Non-alcoholic fatty liver disease (NAFLD) is a type of a disease, showing histological organization similar to those of alcoholic liver disease, although is not associated with alcohol consumption, and is a kind of metabolic syndrome associated with non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinomas. The occurrence of non-alcoholic fatty liver diseases increases with an increase in population with obesity and diabetes. In Korea, the annual incidence has reached approximately 16%.
Non-alcoholic fatty liver disease is known to be caused by various etiologies such as insulin resistance, lipotoxicity and inflammatory responses. Among them, the most common etiology is insulin resistance.
A lot of effort has been made to improve the insulin resistance to prevent/treat non-alcoholic fatty liver disease. For example, currently clinical trials for thiazolidnedinones (TZD) or metformin, a kind of insulin sensitizer, have been actively conducted (see, Hepatology (2003) 38: 1008-17, J Clin Invest (2001) 108: 1167-74).
However, in the case of treatment with the TZD-based drugs, there are disadvantages of a large weight gain and slow fluid flow, and thus the use of such treatment has been known to be impossible for patients with a heart disease. In addition to the TZD-based drugs, clinical tests using GLP-1 receptor agonists such as Victoza or Byetta for non-alcoholic fatty liver disease have been actively conducted. However, in these cases, the in vivo half-life is extremely short, and thus repeated administrations must be made once or at least twice per day, like other polypeptide hormones. Therefore, there is a disadvantage due to inconvenience to patients. Such frequent administrations cause great pain and discomfort to patients. That is, simply using general therapeutic agents for diabetes as a therapeutic agent for non-alcoholic fatty liver disease, through the mechanism of improving insulin resistance has disadvantages such as various side-effects or patient's inconvenience. Due to these factors, when a drug known to be effective in the treatment of diabetes, such as a drug for improving insulin resistance, is directly used as a therapeutic agent for non-alcoholic fatty liver disease, various factors which may result in problems such as side-effects have been known in the art. Hence, whether a drug known to be effective in the treatment of diabetes, such as a drug for improving insulin resistance, can definitely be used as a therapeutic agent for non-alcoholic fatty liver disease, is controversial. Thus, there still remains a need to develop drugs capable of treating non-alcoholic fatty liver disease while securing patient's convenience without side-effects.